EP1263489B1 - Seringue sans aiguille pour l'injection d'un liquide contenu dans une ampoule pre-remplie - Google Patents

Seringue sans aiguille pour l'injection d'un liquide contenu dans une ampoule pre-remplie Download PDF

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Publication number
EP1263489B1
EP1263489B1 EP01903971A EP01903971A EP1263489B1 EP 1263489 B1 EP1263489 B1 EP 1263489B1 EP 01903971 A EP01903971 A EP 01903971A EP 01903971 A EP01903971 A EP 01903971A EP 1263489 B1 EP1263489 B1 EP 1263489B1
Authority
EP
European Patent Office
Prior art keywords
receptacle
downstream
obturator
needleless syringe
syringe according
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
EP01903971A
Other languages
German (de)
English (en)
French (fr)
Other versions
EP1263489A1 (fr
Inventor
Patrick Alexandre
Bernard Brouquieres
Xavière CASTANO
Philippe Gautier
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Crossject Co
Original Assignee
Crossject Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Crossject Co filed Critical Crossject Co
Publication of EP1263489A1 publication Critical patent/EP1263489A1/fr
Application granted granted Critical
Publication of EP1263489B1 publication Critical patent/EP1263489B1/fr
Anticipated expiration legal-status Critical
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/30—Syringes for injection by jet action, without needle, e.g. for use with replaceable ampoules or carpules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/20—Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
    • A61M2005/2006—Having specific accessories
    • A61M2005/2013—Having specific accessories triggering of discharging means by contact of injector with patient body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/20—Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
    • A61M2005/2086—Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically having piston damping means, e.g. axially or rotationally acting retarders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M5/3129—Syringe barrels
    • A61M2005/3132—Syringe barrels having flow passages for injection agents at the distal end of the barrel to bypass a sealing stopper after its displacement to this end due to internal pressure increase
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M2005/3143—Damping means for syringe components executing relative movements, e.g. retarders or attenuators slowing down or timing syringe mechanisms

Definitions

  • the present invention is in the field of needleless, pre-filled and disposable syringes; such syringes are used for intradermal, subcutaneous and intramuscular injections of liquid active principle for therapeutic use in human or veterinary medicine.
  • a first requirement for pre-filled syringes is that of the long-term compatibility, generally three years, between the liquid active ingredient and the reservoir that contains it.
  • Another imperative, related to the pre-filling process, is to have a transparent reservoir to make the regulatory controls of the correct filling of the tank before mounting it in the syringe.
  • the initial phase of the injection is critical for penetration into the skin of the jet or jets of liquid, depending on whether the syringe has one or more injection lines. This last configuration being favorable to reduce the pain.
  • the final bioavailability depends on the good realization of this initial phase, it assumes a fast speed of the liquid in the injection ducts without the multiple jerks of the jets when there is a hammer too important to achieve this setting speed fast.
  • US Patent 4,941,880 describes a syringe very complex from several points of view. First it is a pneumatic motor syringe, to be used several times by changing the ampoule containing the active ingredient.
  • This ampoule containing the active ingredient has two parts juxtaposed.
  • the operator transfers the active ingredient into the downstream part of the ampoule which acts as an intermediate reservoir, by pushing a piston which displaces the liquid and the downstream shutter; this downstream part of the tank is polycarbonate and thick wall, it will withstand the operating pressure generated by the motor device.
  • the operator places the ampoule, thus prepared for injection, into the injection mechanism; upstream of an injection device comprising a single injection pipe which will be fed by a bypass placed at the downstream end of the intermediate injection tank.
  • This arrangement solves the tank resistance problems and, to some extent can reduce the initial saccades of the injection, but with significant pressure drops in a tortuous injection system to feed a single injection pipe.
  • the complexity of the device both in its implementation and in its use is obvious.
  • Patent FR 2 775 603 describes a needleless syringe with a pre-filled ampoule closed at its upstream end by a displaceable shutter and at its downstream end by a multi-jet injector having a central filling orifice closed by a plug after filling of the bulb.
  • US Patent 4,668,223 discloses a syringe with a pre-filled ampoule closed at each of its ends by a displaceable shutter, the upstream end of the bulb receives a guide piece of a piston rod and the downstream end a piece forming a receptacle in which is housed the downstream shutter.
  • the present invention aims to solve all these problems by a device as simple as possible, disposable after the injection and used not only by specialized personnel but also by an ordinary patient.
  • the present invention relates to a needleless syringe comprising a substantially cylindrical reservoir closed by a displaceable upstream shutter, a downstream shutter displaceable and trapping a liquid active principle, the reservoir being initially isolated from an injection system integral with a body, said syringe comprising a motor means for moving the assembly: shutter upstream - liquid - shutter downstream is characterized in that the injection system comprises at least two peripheral injection ducts which are located outside a receptacle of the shutter downstream, the free height of the blind bore of the receptacle allowing the release of the entrances of the peripheral ducts when the shutter downstream is in contact with the bottom of the receptacle.
  • liquid active ingredient or drug
  • the active ingredient may be a solid dissolved in a solvent suitable for injection.
  • the active ingredient may be a solid in pulverulent form suspended, more or less concentrated, in a suitable liquid.
  • the granulometry of the solid active ingredient must be adapted, as well as the shape of the duct to avoid clogging.
  • the tank essentially cylindrical, is type I glass or type II; but he can be in any other transparent material compatible with the active ingredient.
  • the motor means that will act on the upstream shutter may be a mechanical motor: expansion of a compressed spring or pneumatic type: expansion of compressed gas, or pyrotechnic: expansion of combustion gas.
  • the motor means will act on the upstream shutter and move the upstream shutter assembly - liquid - shutter downstream since the liquid is incompressible.
  • the downstream shutter moves and is housed in the blind bore of the receptacle until contact with the bottom of said receptacle.
  • the height of this bore is such that when the downstream shutter is in contact with the bottom of the receptacle the inlet of the injection ducts, on the periphery of the receptacle, are disengaged; the liquid is repressed and is injected by the movement of the upstream shutter which continues until the emptying of the tank: the upstream shutter is then in contact with the downstream shutter.
  • the needleless syringe is such that the reservoir of liquid active ingredient is housed in the body on which is fixed the injection system.
  • the receptacle in which the downstream obturator is housed, is a part of the body of the syringe.
  • the receptacle of the downstream shutter comprises at least one means for damping the impact the shutter downstream before stopping in the bottom of the receptacle. This damping, which avoids the bouncing of the shutter is intended to avoid injection jerks at the beginning of operation.
  • the downstream shutter comprises, on its side facing the receptacle, a recess of form conjugated to that of a stud integral with the bottom of the receptacle. During its displacement the downstream shutter will be entrenched by this recess on the stud.
  • This fitting absorbs the impact energy of the shutter on the bottom of the receptacle.
  • this fitting is rendered irreversible, for example, by a bead or notches arranged around the stud.
  • the downstream shutter can be housed in a receptacle of very slightly frustoconical shape with a large section at the entrance of the receptacle and a smaller section at the bottom. The deformation of the shutter to be housed in this receptacle dampens the impact.
  • the downstream shutter comprises a compressible part.
  • the downstream shutter is housed in the bore of the receptacle by crushing this compressible portion: the depth of the bore is less than the height of the shutter before deformation. It is the crushing of this deformable part which dampens the impact of the downstream shutter.
  • the motor means acts directly on the upstream shutter.
  • the motor means acts on the upstream shutter by means of a piston.
  • the motor means is a generator of the pneumatic type or the pyrotechnic type.
  • a first low-pressure, low-speed phase is carried out to move the "upstream-liquid shutter-downstream shutter” assembly and engage, without shock, the downstream shutter. in the receptacle then a second high pressure phase for high speed injection.
  • the motor means is a pyrotechnic gas generator.
  • a pyrotechnic gas generator Such a device is compact, powerful and above all very reliable: the storage time of this type of generator is much greater than the period of preservation of the active ingredient.
  • the reservoir and the body of the syringe form a single unit, compatible for a long time with the active ingredient and resistant to high pressures during operation.
  • the reservoir is hooped in the body by an intermediate material during assembly, on the motor means, the body of the syringe with the reservoir.
  • the body of the syringe is made of a transparent material which allows the display of the active ingredient reservoir until the moment of injection.
  • the body has at least one viewing window of the contents of the reservoir, when the material of the body of the syringe is not transparent.
  • the piston acting on the upstream obturator serves as an indicator of the operation of the syringe appearing in the transparent part or the window of the body of the syringe.
  • the upstream shutter can also fulfill this function.
  • the needleless syringe with several injection lines in the various embodiments of the invention solves the problems posed.
  • the long-term compatibility between the liquid active ingredient and the reservoir containing it by the choice of the shape and materials of the tank. Holding the tank at the high operating pressure by the different type of tank mounting in the body. Performing an injection without saccades at the beginning of the phase of speed of the liquid by the operation of the device and the damping of the impact.
  • the present invention has the advantage of allowing two parts to be separated in the device.
  • a part which will be said pharmaceutical part comprising the body and the reservoir with the movable shutters upstream and downstream: this subset can be treated under the conditions of the pharmaceutical industry including sterilization and asepsis.
  • This subset will be integrated with the rest of the syringe, whose elements have been assembled elsewhere, this assembly being done under the conditions less severe than those related to the pharmaceutical industry.
  • this configuration has the advantage of avoiding any leakage of liquid by the injection ducts before the injection is made. Indeed the agitation of the device is frequently carried out, or even recommended to examine the turbidity of the liquid or homogenize the mixture when the liquid has particles in suspension. The fact that the active principle is isolated, before injection, the conduits provides ultimate protection against this risk of loss.
  • FIG. 1 shows a longitudinal section of a syringe according to a first embodiment.
  • FIG. 2 shows the partial view of the downstream end of a syringe in which the downstream obturator has a compressible part.
  • Figures 3 and 4 show a partial view of the downstream end of a syringe according to another variant, respectively before and after operation, in this embodiment the downstream shutter comprises a recess.
  • Figure 5 shows an alternative with a stepped piston to move the upstream and downstream shutters.
  • Figure 1 shows a partial longitudinal section of a syringe according to the invention, it is shown vertical, the injection system directed downwards.
  • the syringe 1 comprises a body 2 in which is housed a reservoir 3 containing the liquid active principle 6. At the downstream end of the body 2 is placed a receptacle 7 comprising, for example, three injection conduits such as the conduit 8.
  • the injection system is covered with an external protection to ensure the asepsis of the syringe: this protection comprises an elastomer membrane applied to the outer face of the injector by a thin metal cap, crimped around this end of the syringe. the syringe. This protection will be removed before injection.
  • the body 2 of the syringe is attached to a motor means 70 which, in this example, is a pyrotechnic gas generator, it will be described later.
  • the body 2 of the syringe has two diametrically opposed windows for the visualization of the active principle contained in the reservoir 3: they are simply two oblong openings 12 in the body. Downstream of the body 2 of the syringe is fitted, in a bore of appropriate shape, a receptacle 7 cylindro-conical which will be described later. Bearing on this receptacle 7 and centered downstream of the body 2 is positioned a glass reservoir 3; this reservoir is a tube surrounded by a transparent intermediate material 9.
  • the reservoir 3 is essentially a tube closed at both ends by movable shutters upstream 4 and downstream 5; these shutters are preferably piston stoppers usually used in syringes: they are parts obtained by molding elastomers compatible for a long time with the active principle: each piece integrates the functions of piston and sealing by making beads or lips (not detailed in the figures).
  • the elastomers usually used for the manufacture of these parts are for example chlorobutyl or bromobutyl, whose Shore hardness is set between about 45 and about 70. These parts can receive surface treatments including to facilitate their movement in the tubular reservoir.
  • the plug-piston When free, the plug-piston has a diameter about 10 percent greater than the inside diameter of the tube that will receive it, the height of the plug-piston is about 0.5 to 0.8 times this diameter .
  • the plunger plug is engaged in the tube, due to deformations, its height is about 0.6 to about 1.0 times the inner diameter of the reservoir.
  • the receptacle 7 is a piece of cylindro-conical outer shape which has a central bore 10 into which the downstream obturator 5 will be received. On its periphery the receptacle comprises three injection conduits of which only one, reference 8 , is visible on this section. The diameter of the bore is equal to that of the tank. The free height of the blind bore 10 of the receptacle 7 is equal to that of the downstream shutter 5 mounted in the reservoir 3.
  • the inlet 8a (reservoir side 3) of the injection pipes 8 is placed in communication with the liquid 6; the liquid flows with a speed corresponding to the pressure transmitted by the upstream shutter 4.
  • the motor means acts on the upstream shutter by means of a piston 11 of effective section equal to that of the upstream shutter 5.
  • This piston 11 is in contact with the upstream shutter 5 there therefore has no shock effect or ram at the beginning of operation.
  • This piston 11 thanks to its sealing system prevents the gases produced by the combustion of the load 72 from coming into contact with the upstream shutter and therefore possible deterioration thereof and leakage of gas to the active principle contained in The reservoir.
  • This piston 11, of a suitable color can also serve as an indicator of operation appearing in the viewing windows of the body 2 of the syringe.
  • the pyrotechnic generator 70 comprises in the body 71 above the piston a pyrotechnic charge 72 whose combustion is initiated by a primer 80 impacted by a striker 74.
  • the primer 73 is housed in a door -amorce.
  • the striker 74 is retained in the striker guide 75 secured by screwing the body 71 by at least one ball, such as the ball 77, partially engaged in a groove of the striker.
  • the percussion device comprises a pusher 78 with a groove 79 and an inner spring 76.
  • the pusher 78 slides on the outside of the striker guide 75 and is not held pins moving in lateral grooves. This pusher 78 is here the trigger member.
  • initiation devices other than the striker device described here. Without going into details and without wanting to be exhaustive, we will cite as examples of initiation devices with electric battery or piezoelectric initiation devices.
  • the pyrotechnic gas generator may be replaced by a gas generator consisting of a compressed gas reservoir closed by a quick-opening valve.
  • the trigger member will open said valve, compressed gas tank will relax and act on the thrust means.
  • the operator presses, with his thumb, the pusher 78 which sinks in compression the spring 76.
  • the pusher moves until the groove 78 reaches the height of the throat of the striker 74, the balls, such as the ball 77, retaining the striker 74, are released in the groove 79 and release the striker that will violently impact the primer 73, whose initiation ignites the pyrotechnic charge 72.
  • the striker 74 resting on the primer holder 80 ensures the maintenance in place of the primer and sealing: the combustion gases do not not going back to the pusher.
  • FIG. 2 shows the partial view of another embodiment of the invention wherein the downstream shutter 25 is partially compressible.
  • This shutter before operation has a height or thickness greater than the height of the blind bore 21 of the receptacle 27.
  • the motor means moves the upstream shutter assembly 24 - liquid 26 - downstream shutter 25; the downstream shutter is housed in the blind bore 21 of the receptacle then comes into contact with the bottom and under the effect of pressure, the compressible portion crushes releases the inputs of the injection ducts and allows the passage of the liquid.
  • the deformation by partial compression of the downstream shutter 25 in the blind bore of the receptacle dampens the shock due to the shutdown of the downstream shutter and prevents the ejection of the liquid by multiple saccades.
  • the downstream shutter 25 consists, for example, of two layers of different materials: reservoir side a deformable elastomeric layer 29 but incompressible, compatible with the active ingredient, and then a layer of a highly compressible material 29a that goes crush when the downstream shutter engages to the bottom of the receptacle.
  • the downstream obturator is made of a single elastomer compatible with the active principle but has on its lower part, coming into contact with the bottom of the receptacle, at least one cavity which will be closed by the deformation of the elastomer during the engagement of the downstream shutter in the receptacle. This deformation dampens the impact of the shutter and also reduces the volume occupied by the shutter.
  • Figure 3 shows, in partial view, another embodiment of the invention which differs from the previous by the particular form of the downstream shutter and the mounting of the reservoir in the body of the syringe.
  • the body 32 of the syringe is made of a transparent material and sufficiently thick to withstand high operating pressures.
  • a cylindro-conical receptacle 37 is fitted into the downstream end of the body 32.
  • the reservoir 33 containing the liquid active ingredient and closed by the upstream and downstream 35 and 35 obturators, is housed in the body 32.
  • the body 32 serves as reinforcement at tank 33 at the time of injection.
  • Another particularity of this example is the recess 36 on the downstream face of the displaceable shutter 35 and the stud 39 fixed in the bottom of the receptacle.
  • the recess 36 and the stud 39 have shapes that allow their engagement when the downstream shutter 35 moves under the effect of the pressure transmitted by the piston 31. This interlock absorbs energy and dampens the impact of the shutter 35 on the bottom of the receptacle 37: there is no rebound of the downstream shutter 35 which remains fitted on the stud 39.
  • the damping of the downstream shutter in the receptacle can also be achieved by a receptacle of slightly frustoconical shape in which is housed and deformed the downstream shutter.
  • the damping can also be carried out pneumatically by at least one calibrated vent hole which controls the flow rate of air discharged by the downstream shutter during its displacement in the receptacle.
  • FIG. 4 shows, in partial view, the position of the downstream 35 and upstream shutters 34 during the injection.
  • the downstream shutter 35 is in the blind bore of the receptacle 37, it is engaged by its recess 36 on the stud 39 fixed on the bottom of the receptacle: this fitting is rendered irreversible by a bead surrounding the stud 39.
  • the upstream shutter 34 pushed by the piston 31, discharges the liquid.
  • This FIG. 4 illustrates an injection in progress: the shutter 35 bears on the bottom of the receptacle 37 and releases the inlets 38a of the injection ducts 38 and this, as long as the upstream shutter 34 has not finished also his stroke to come to bear on the downstream shutter 35.
  • FIG. 5 shows another embodiment of the invention which differs from the example of FIG. 2 by the use of a stepped piston 51.
  • the piston 51 comprises a small section head which will transmit a moderate force, at the beginning of operation, for the setting in motion and acceleration of the assembly "shutter upstream 54 - liquid 56 - shutter downstream 55".
  • the displacement lengths are chosen such that when the small section head is disengaged, more precisely when the upper seal of the piston 51 ceases to be effective, the downstream shutter 55 is entirely housed in the receptacle 57, the gases of the generator will then act on the large section of the piston 51 subjecting the liquid 56 to a high pressure and as it is placed in communication with the openings 58a of the injection pipes 58 the liquid 56 will be injected at high speed which is favorable piercing the skin and good biosavailability of the active ingredient.

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  • Health & Medical Sciences (AREA)
  • Vascular Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
EP01903971A 2000-02-11 2001-01-26 Seringue sans aiguille pour l'injection d'un liquide contenu dans une ampoule pre-remplie Expired - Lifetime EP1263489B1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR0001721A FR2804869B1 (fr) 2000-02-11 2000-02-11 Seringue sans aiguille pour l'injection d'un liquide contenu dans une ampoule pre-remplie
FR0001721 2000-02-11
PCT/FR2001/000250 WO2001058512A1 (fr) 2000-02-11 2001-01-26 Seringue sans aiguille pour l'injection d'un liquide contenu dans une ampoule pre-remplie

Publications (2)

Publication Number Publication Date
EP1263489A1 EP1263489A1 (fr) 2002-12-11
EP1263489B1 true EP1263489B1 (fr) 2006-04-05

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Application Number Title Priority Date Filing Date
EP01903971A Expired - Lifetime EP1263489B1 (fr) 2000-02-11 2001-01-26 Seringue sans aiguille pour l'injection d'un liquide contenu dans une ampoule pre-remplie

Country Status (26)

Country Link
US (1) US7056300B2 (pl)
EP (1) EP1263489B1 (pl)
JP (1) JP3718167B2 (pl)
KR (1) KR100458062B1 (pl)
CN (1) CN1168508C (pl)
AT (1) ATE322299T1 (pl)
AU (1) AU765358B2 (pl)
BR (1) BR0108389B1 (pl)
CA (1) CA2398552C (pl)
CZ (1) CZ300270B6 (pl)
DE (1) DE60118532T2 (pl)
DZ (1) DZ3291A1 (pl)
ES (1) ES2259023T3 (pl)
FR (1) FR2804869B1 (pl)
HK (1) HK1052474B (pl)
HU (1) HU226759B1 (pl)
IL (2) IL150815A0 (pl)
IS (1) IS2292B (pl)
MA (1) MA25708A1 (pl)
MX (1) MXPA02007745A (pl)
NO (1) NO330380B1 (pl)
PL (1) PL197494B1 (pl)
RU (1) RU2218942C1 (pl)
UA (1) UA69494C2 (pl)
WO (1) WO2001058512A1 (pl)
ZA (1) ZA200206303B (pl)

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JP2017533238A (ja) 2014-10-28 2017-11-09 アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル 抗原特異的寛容のための組成物及び方法
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AU3191501A (en) 2001-08-20
CN1398191A (zh) 2003-02-19
WO2001058512A1 (fr) 2001-08-16
NO330380B1 (no) 2011-04-04
CA2398552C (fr) 2007-07-03
CZ300270B6 (cs) 2009-04-08
BR0108389B1 (pt) 2009-01-13
ZA200206303B (en) 2003-10-16
PL197494B1 (pl) 2008-04-30
UA69494C2 (uk) 2004-09-15
NO20023794D0 (no) 2002-08-09
US20030050596A1 (en) 2003-03-13
KR20020087051A (ko) 2002-11-21
FR2804869A1 (fr) 2001-08-17
IS6473A (is) 2002-07-16
HK1052474A1 (en) 2003-09-19
US7056300B2 (en) 2006-06-06
IL150815A (en) 2006-04-10
DZ3291A1 (fr) 2001-08-16
HUP0204453A2 (en) 2003-03-28
DE60118532D1 (de) 2006-05-18
MA25708A1 (fr) 2003-04-01
IS2292B (is) 2007-10-15
JP3718167B2 (ja) 2005-11-16
PL357717A1 (pl) 2004-07-26
FR2804869B1 (fr) 2002-05-17
HK1052474B (zh) 2005-03-04
RU2218942C1 (ru) 2003-12-20
BR0108389A (pt) 2003-03-11
IL150815A0 (en) 2003-02-12
HU226759B1 (en) 2009-09-28
CA2398552A1 (fr) 2001-08-16
DE60118532T2 (de) 2006-11-23
ATE322299T1 (de) 2006-04-15
RU2002124138A (ru) 2004-02-20
ES2259023T3 (es) 2006-09-16
KR100458062B1 (ko) 2004-11-26
EP1263489A1 (fr) 2002-12-11
MXPA02007745A (es) 2004-09-10
JP2003530147A (ja) 2003-10-14
NO20023794L (no) 2002-09-30
CN1168508C (zh) 2004-09-29
AU765358B2 (en) 2003-09-18

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